Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs

Muhammad Tukur Ibrahim; Muhammad Suleiman Darma; Sanı Uba

doi:10.54565/jphcfum.1721789

Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs

Abstract

Cystic fibrosis (CF) is a life-shortening genetic disorder caused by mutations in the CFTR gene, leading to dysfunctional chloride ion transport and associated complications. This study employs computational chemistry to explore the molecular mechanisms underlying CF and to aid the development of targeted therapeutics. Twenty-seven ligand derivatives from 3-(2-benzyloxyphenyl) isoxazoles and isoxazolines previously reported as CFTR activators were analyzed and compared to genistein, a known CF therapeutic. Ligand structures were optimized using Density Functional Theory (DFT), and molecular descriptors were computed with PaDEL software. Using Genetic Function Approximation (GFA) via Material Studio, Quantitative Structure-Activity Relationship (QSAR) models were developed to correlate molecular features with biological activity (pIC₅₀). The top model (R² = 0.974) demonstrated high predictive power and reliability, validated through cross-validation and applicability domain analysis. Key descriptors such as SpDiam_Dt, GATS4v, and MATS7i significantly influenced model performance, offering insights into molecular traits critical for CF treatment efficacy. These findings highlight the potential of computational approaches in accelerating drug discovery for cystic fibrosis by identifying and optimizing promising lead compounds.

Keywords

References

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Details

Primary Language

English

Subjects

Condensed Matter Modelling and Density Functional Theory

Journal Section

Research Article

Authors

Muhammad Tukur Ibrahim
0000-0002-6146-5667
Nigeria

Muhammad Suleiman Darma ^*
0000-0001-8762-1077
Nigeria

Sanı Uba
0000-0001-9595-6897
Nigeria

Publication Date

December 23, 2025

Submission Date

June 17, 2025

Acceptance Date

November 30, 2025

Published in Issue

Year 2025 Volume: 8 Number: 2

DOI

https://doi.org/10.54565/jphcfum.1721789

IZ

https://izlik.org/JA47UW65TN

Cite

RIS / Bibtex

APA

Ibrahim, M. T., Suleiman Darma, M., & Uba, S. (2025). Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs. Journal of Physical Chemistry and Functional Materials, 8(2), 158-170. https://doi.org/10.54565/jphcfum.1721789

AMA

1.Ibrahim MT, Suleiman Darma M, Uba S. Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs. Journal of Physical Chemistry and Functional Materials. 2025;8(2):158-170. doi:10.54565/jphcfum.1721789

Chicago

Ibrahim, Muhammad Tukur, Muhammad Suleiman Darma, and Sanı Uba. 2025. “Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs”. Journal of Physical Chemistry and Functional Materials 8 (2): 158-70. https://doi.org/10.54565/jphcfum.1721789.

EndNote

Ibrahim MT, Suleiman Darma M, Uba S (December 1, 2025) Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs. Journal of Physical Chemistry and Functional Materials 8 2 158–170.

IEEE

[1]M. T. Ibrahim, M. Suleiman Darma, and S. Uba, “Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs”, Journal of Physical Chemistry and Functional Materials, vol. 8, no. 2, pp. 158–170, Dec. 2025, doi: 10.54565/jphcfum.1721789.

ISNAD

Ibrahim, Muhammad Tukur - Suleiman Darma, Muhammad - Uba, Sanı. “Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs”. Journal of Physical Chemistry and Functional Materials 8/2 (December 1, 2025): 158-170. https://doi.org/10.54565/jphcfum.1721789.

JAMA

1.Ibrahim MT, Suleiman Darma M, Uba S. Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs. Journal of Physical Chemistry and Functional Materials. 2025;8:158–170.

MLA

Ibrahim, Muhammad Tukur, et al. “Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs”. Journal of Physical Chemistry and Functional Materials, vol. 8, no. 2, Dec. 2025, pp. 158-70, doi:10.54565/jphcfum.1721789.

Vancouver

1.Muhammad Tukur Ibrahim, Muhammad Suleiman Darma, Sanı Uba. Utılızıng Computatıonal Chemıstry To Unravel The Molecular Mechanısms of Cystıc Fıbrosıs Mutatıons And Develop Targeted Therapeutıcs. Journal of Physical Chemistry and Functional Materials. 2025 Dec. 1;8(2):158-70. doi:10.54565/jphcfum.1721789